eBriefing

Global Metabolite Profiling: The Fast-Track for Functional Genomics

Global Metabolite Profiling
Reported by
Megan Stephan

Posted May 11, 2011

Overview

Every metabolic process leaves behind a chemical footprint—a record of the reactions that occurred and the substances that entered or exited each cell. Of course, this footprint is transient, lasting only until other metabolic processes leave their own mark on enzyme, lipid, small molecule, and other metabolite levels. Metabolomics aims to exploit the temporal and spatial specificity of metabolic footprints to characterize disease states, identify biomarkers of risk and progression, predict treatment response, illuminate disease etiology, and, on a more fundamental level, understand the complex processes and components of metabolism.

Global metabolite profiling offers the breadth and the temporal and spatial specificity to elucidate underlying mechanisms of disease pathology and to advance understanding of multi-faceted conditions such as chronic pain and multiple sclerosis. On February 11, 2011 the New York Academy of Sciences held Global Metabolite Profiling: The Fast-Track for Functional Genomics, a forum for researchers in metabomics to discuss the latest discoveries in and the future of the field. Presenters covered applications of metabolomics methods to validating functional assignments for orphan enzymes, to identifying biomarkers of breast cancer development, and to everything in between. The symposium revealed the great strides that have already been made through studies of metabolites, the complex output of an even more complex set of regulatory interactions.

Use the tabs above to find a meeting report and multimedia from this event.

 

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Silver Sponsor

  • Agilent Technologies

Grant Support

Supported by an educational grant from the Celgene Corporation.

Web Sites

The Fiehn Group

Siuzdak: Scripps Center for Metabolomics and Mass Spectroscopy

The Guengerich Group

Guengerich at the Vanderbilt-Ingram Cancer Center

The Saghatelian Group

The Zamboni Group

Building Blocks, Biological Pathways, and Networks
NIH Roadmap that includes Metabolomics Technology Development.

Human Metabolome Database
Freely available electronic database containing detailed information about small molecule metabolites found in the human body.

The Metabolomics Society
International society dedicated to promoting the growth, use and understanding of metabolomics in the life sciences.

Metabolism: Special Online Collection at Science Magazine
Collection of articles on the resurgence of metabolism as a topic of scientific interest.

METAcancer
Research consortium dedicated to the identification and validation of new breast cancer biomarkers based on integrated metabolomics.

METLIN: Metabolite and Tandem MS Database

Molecule of the Month: Cytochrome P450
European Bioinformatics Institute article on cytochrome P450s.

NURSA: Nuclear Receptor Signaling Atlas
Information portal for researchers interested in nuclear receptor signaling.

What is Mass Spectrometry?


Journal Articles

Fiehn

Abate S, Ahn YG, Kind T, et al. 2010. Determination of elemental compositions by gas chromatography/time-of-flight mass spectrometry using chemical and electron ionization. Rapid Commun. Mass Spectrom. 24: 1172-80.

Fiehn O, Garvey WT, Newman JW, et al. 2010. Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women. PLoS One 5: e15234.

Hilvo M, Denkert C, Lehtinen L, et al. 2011. Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression. Cancer Res. epub ahead of print.

Ji Y, Hebbring S, Zhu H, et al. 2011. Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics. Clin. Pharmacol. Ther. 89: 97-104.

Kind T, Fiehn O. 2009. What are the obstacles for an integrated system for comprehensive interpretation of cross-platform metabolic profile data? Bioanalysis 1: 1511-4.

Kind T,Fiehn O. 2010. Advances in structure elucidation of small molecules using mass spectrometry. Bioanal. Rev. 2: 23-60.

Reichenbach SE, Tian X, Tao Q, et al. 2011. Informatics for cross-sample analysis with comprehensive two-dimensional gas chromatography and high-resolution mass spectrometry (GCxGC-HRMS). Talanta. 83: 1279-88.

Robertson DG, Ruepp SU, Stryker SA, et al. 2011. Metabolomic and transcriptomic changes induced by overnight (16 h) fasting in male and female Sprague-Dawley rats. Chem. Res. Toxicol. epub ahead of print.

Taylor SL, Ganti S, Bukanov NO, et al. 2010. A metabolomics approach using juvenile cystic mice to identify urinary biomarkers and altered pathways in polycystic kidney disease. Am. J. Physiol. Renal Physiol. 298: F909-22.

Wohlgemuth G, Haldiya PK, Willighagen E, et al. 2010. The Chemical Translation Service—a web-based tool to improve standardization of metabolomic reports. Bioinformatics 26: 2647-8.

Guengerich

Cheng Q, Lamb DC, Kelly SL, et al. 2010. Cyclization of a cellular dipentaenone by Streptomyces coelicolor cytochrome P450 154A1 without oxidation/reduction. J. Am. Chem. Soc. 132: 15173-5.

Guengerich FP. 2011. Mechanisms of drug toxicity and relevance to pharmaceutical development. Drug Metab. Pharmacokinet. 26: 3-14.

Guengerich FP, Sohl CD,Chowdhury G. 2011. Multi-step oxidations catalyzed by cytochrome P450 enzymes: Processive vs. distributive kinetics and the issue of carbonyl oxidation in chemical mechanisms. Arch. Biochem. Biophys. 507: 126-34.

Guengerich FP, Tang Z, Cheng Q, et al. 2011. Approaches to deorphanization of human and microbial cytochrome P450 enzymes. Biochim. Biophys. Acta. 1814: 139-45.

Guengerich FP, Tang Z, Salamanca-Pinzon SG, et al. 2010. Characterizing proteins of unknown function: orphan cytochrome p450 enzymes as a paradigm. Mol. Interv. 10: 153-63.

Robert C, Wilson CS, Guengerich FP, et al. 2010. Evolution of the scientific literature of cytochrome P450 from 1977 to 2008. Curr. Drug Metab. 11: 162-70.

Shinkyo R, Guengerich FP. 2011. Cytochrome P450 7A1 cholesterol 7alpha-hydroxylation: individual reaction steps in the catalytic cycle and rate-limiting ferric iron reduction. J. Biol. Chem. 286: 4632-43.

Shinkyo R, Guengerich FP. 2011. Inhibition of human cytochrome P450 3A4 by cholesterol. J. Biol. Chem., epub ahead of print.

Tang Z,Guengerich FP. 2010. Dansylation of unactivated alcohols for improved mass spectral sensitivity and application to analysis of cytochrome P450 oxidation products in tissue extracts.Anal. Chem. 82: 7706-12.

Xiao Y, Shinkyo R,Guengerich FP. 2011. Cytochrome P450 2S1 is Reduced by NADPH-Cytochrome P450 Reductase. Drug Metab. Dispos., epub ahead of print.

Saghatelian

Homan EA, Kim YG, Cardia JP, et al. 2011. Monoalkylglycerol ether lipids promote adipogenesis.J. Am. Chem. Soc. 133: 5178-81.

Kim YG, Lou AC, Saghatelian A. 2011. A metabolomics strategy for detecting protein-metabolite interactions to identify natural nuclear receptor ligands. Mol. Biosyst. 7: 1046-9.

MacBeath G,Saghatelian A. 2009. The promise and challenge of '-omic' approaches. Curr. Opin. Chem. Biol. 13: 501-2.

Tagore R, Thomas HR, Homan EA, et al. 2008. A global metabolite profiling approach to identify protein-metabolite interactions. J. Am. Chem. Soc. 130: 14111-3.

Vinayavekhin N, Homan EA, Saghatelian A. 2010. Exploring disease through metabolomics. ACS Chem. Biol. 5: 91-103.

Vinayavekhin N, Saghatelian A. 2010. Untargeted metabolomics. Curr. Protoc. Mol. Biol. Chapter 30: Unit 30 1 1-24.

Siuzdak

Benton HP, Wong DM, Trauger SA, et al. 2008. XCMS2: processing tandem mass spectrometry data for metabolite identification and structural characterization. Anal. Chem. 80: 6382-9.

Crews B, Wikoff WR, Patti GJ, et al. 2009. Variability analysis of human plasma and cerebral spinal fluid reveals statistical significance of changes in mass spectrometry-based metabolomics data. Anal. Chem. 81: 8538-44.

Greving MP, Patti GJ,Siuzdak G. 2011. Nanostructure-initiator mass spectrometry metabolite analysis and imaging. Anal. Chem. 83: 2-7.

Patti GJ, Shriver LP, Wassif CA, et al. 2010. Nanostructure-initiator mass spectrometry (NIMS) imaging of brain cholesterol metabolites in Smith-Lemli-Opitz syndrome. Neuroscience 170: 858-64.

Patti GJ, Woo HK, Yanes O, et al. 2010. Detection of carbohydrates and steroids by cation-enhanced nanostructure-initiator mass spectrometry (NIMS) for biofluid analysis and tissue imaging. Anal. Chem. 82: 121-8.

Tautenhahn R, Patti GJ, Kalisiak E, et al. 2011. metaXCMS: second-order analysis of untargeted metabolomics data. Anal. Chem. 83: 696-700.

Wikoff WR, Anfora AT, Liu J, et al. 2009. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc. Natl. Acad. Sci. USA 106: 3698-703.

Yanes O, Clark J, Wong DM, et al. 2010. Metabolic oxidation regulates embryonic stem cell differentiation. Nat. Chem. Biol. 6: 411-7.

Yanes O, Tautenhahn R, Patti GJ, et al. 2011. Expanding coverage of the metabolome for global metabolite profiling. Anal. Chem. 83: 2152-61.

Yanes O, Woo HK, Northen TR, et al. 2009. Nanostructure initiator mass spectrometry: tissue imaging and direct biofluid analysis. Anal. Chem. 81: 2969-75.

Zamboni

Buescher JM, Moco S, Sauer U, et al. 2010. Ultrahigh performance liquid chromatography-tandem mass spectrometry method for fast and robust quantification of anionic and aromatic metabolites. Anal. Chem. 82: 4403-12.

Buscher JM, Czernik D, Ewald JC, et al. 2009. Cross-platform comparison of methods for quantitative metabolomics of primary metabolism. Anal. Chem. 81: 2135-43.

Canelas AB, Harrison N, Fazio A, et al. 2010. Integrated multilaboratory systems biology reveals differences in protein metabolism between two reference yeast strains. Nat. Commun. 1: 145.

Ewald JC, Heux S,Zamboni N. 2009. High-throughput quantitative metabolomics: workflow for cultivation, quenching, and analysis of yeast in a multiwell format. Anal. Chem. 81: 3623-9.

Fendt SM, Buescher JM, Rudroff F, et al. 2010. Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity. Mol. Syst. Biol. 6: 356.

Kummel A, Ewald JC, Fendt SM, et al. 2010. Differential glucose repression in common yeast strains in response to HXK2 deletion. FEMS Yeast Res. 10: 322-32.

Zamboni N. 2011. 13C metabolic flux analysis in complex systems. Curr. Opin. Biotechnol. 22: 103-8.

Zamboni N, Fendt SM, Ruhl M, et al. 2009. (13)C-based metabolic flux analysis. Nat. Protoc. 4: 878-92.

Zamboni N,Sauer U. 2009. Novel biological insights through metabolomics and 13C-flux analysis. Curr. Opin. Microbiol. 12: 553-8.


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Organizers

Steven Gross
Steven Gross, PhD

Weill Cornell Medical College
e-mail | website

Steven S. Gross is Professor of Pharmacology and Director of the Mass Spectrometry Core Facility. Gross's expertise is in pharmacology, and cell and structural biology, particularly in relation to the role of nitric oxide (NO) as a signaling molecule. In the late 1980s, Gross and colleagues made the initial identification of L-arginine as the precursor of NO in blood vessels. They were also first to establish that NOS inhibition elevates blood pressure in animals, demonstrating that NO plays a physiological role in controlling blood pressure and vascular tone. Since then, research efforts have predominantly focused on elucidating the enzymes and mechanisms that regulate NO synthesis in cells. Gross has authored or coauthored more than 90 research publications and 40 book chapters, review articles and books in the area of NO biology. He is an active member of NIH Study Sections and is a founder and Board Director of the Nitric Oxide Society, a group that organizes the major annual international meetings on the subject of NO and publishes a peer-reviewed scientific journal with novel reports on NO biology and chemistry. Gross received his PhD in Biomedical Science from the Mount Sinai School of Medicine in New York City.

Jennifer Henry, PhD

The New York Academy of Sciences
e-mail


Speakers

Oliver Fiehn
Oliver Fiehn, PhD

University of California, Davis
e-mail | website | publications

Oliver Fiehn is a Professor at the University of California, Davis in the Genome Center. After obtaining his PhD from the Technical University of Berlin, Germany in Analytical Toxicology, he joined the Max-Planck Institute of Molecular Plant Physiology in 1998 to contribute to the field of metabolomics. He accepted an offer to join UC Davis in 2004 and has since focused on metabolomics in human diseases, analytical techniques, and databases. He has published more than 100 papers in peer-reviewed journals and is a member of the board of the directors of the Metabolomics Society, and member of the editorial boards of several journals, among them the Journal of Biological Chemistry. Fiehn's main research field is the mass spectrometry and its use for metabolite analysis, in conjunction with bioinformatics approaches to utilize metabolic data for plant and animal research.

F. Peter Guengerich

F. Peter Guengerich, PhD

Vanderbilt University School of Medicine
e-mail | website | publications

F. Peter Guengerich is a Professor of Biochemistry at Vanderbilt University School of Medicine. He received his BS from the University of Illinois in 1970 and then did his graduate work at Vanderbilt University, receiving his PhD in Biochemistry in 1973. After two years as a research fellow at the University of Michigan, he was hired as Assistant Professor of Biochemistry at Vanderbilt in 1975 and has been on faculty since then, and he attained the rank of Professor in 1983. Guengerich has been Director of the Center in Molecular Toxicology, an interdepartmental program at Vanderbilt, since 1981. In 2010 he assumed the position of Interim Chair of the Department of Biochemistry.

His own research laboratory deals with the chemical and biological mechanisms by which drugs and cancer-causing chemicals are processed and the relevance to drug development, toxicity, and disease. A major area of interest is the enzymology of cytochrome P450 enzymes, which are the major catalysts involved in the metabolism of drugs. He is an author or co-author of 603 original research articles and 176 invited reviews. He is an associate editor of The Journal of Biological Chemistry and Chemical Research in Toxicology.

Alan Saghatelian

Alan Saghatelian, PhD

Harvard University
e-mail | website | publications

Alan Saghatelian grew up in southern California and attended UCLA as an undergrad where he graduated with a degree in chemistry. He got his first taste of research working with Professor Craig Merlic in the area of organometallic chemistry and synthetic chemistry. For graduate school, Saghatelian attended The Scripps Research Institute in La Jolla where he moved into biochemical problems such as the molecular mechanisms that spawned life and allosteric regulation of enzymes through protein engineering. It was at TSRI that Saghatelian became more interested in biomedical research and he remained at TSRI for a postdoc with Professor Benjamin Cravatt where he developed (with Gary Siuzdak's help) methods for global metabolite profiling of lipids to identify novel mammalian lipids and substrates for enzymes. In 2006, Saghatelian started in the chemistry department at Harvard where he has continued to extend the utility of these methods to biology. He is currently an Associate Professor of Chemistry and Chemical Biology.

Gary Siuzdak

Gary Siuzdak, PhD

The Scripps Research Institute, California
e-mail | website | publications

Gary Siuzdak is Director of the Scripps Center for Metabolomics and Professor of Chemistry and Molecular Biology at The Scripps Research Institute in La Jolla, California. He is also Faculty Guest at Lawrence Berkeley National Laboratory and served as Vice President of the American Society for Mass Spectrometry. His research includes developing novel approaches to unbiased metabolomics, the development of nanostructure-based platforms for mass spectrometry imaging, novel approaches to virus characterization and inhibition, and mass-based inhibitor-enzyme screening. He has over 170 peer-reviewed publications and two books, the latest being The Expanding Role of Mass Spectrometry in Biotechnology, 2nd Edition 2006.

Nicola Zamboni

Nicola Zamboni, PhD

Institute of Molecular Systems Biology, ETH Zurich
e-mail | website | publications

Nicola Zamboni is a principal investigator at the Institute of Molecular Systems Biology of ETH Zurich since 2005. He graduated in group of Jay Bailey at the Institute of Biotechnology of ETH Zurich, where he also received his PhD in 2003 in the field of Metabolic Engineering. In 2004, he moved to Stanford University to devise metabolomics-derived approaches for unraveling causes of intracellular metabolic changes. His research in this area continues currently at ETH Zurich, where his work builds on metabolomics, 13C flux analysis, and computational biology.

Research in his group ultimately aims at identifying interaction networks involving metabolism in complex systems, spanning from microorganisms in natural environments to pathogens and higher cells.


Megan Stephan

Megan Stephan studied transporters and ion channels at Yale University for nearly two decades before giving up the pipettor for the pen. She specializes in covering research at the interface between biology, chemistry and physics. Her work has appeared in The Scientist and Yale Medicine. Stephan holds a PhD in biology from Boston University.



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Sponsors

Silver Sponsor

  • Agilent Technologies

Grant Support

Supported by an educational grant from the Celgene Corporation.



Please complete this short survey after viewing the eBriefing.